The molecular genetic changes of human pancreatic carcinoma are largely unknown but there is compelling evidence that undiscovered tumor suppressor genes are involved. Tumor suppressor genes are found frequently at sites of genetic less in human cancers. Two molecular genetic techniques have been shown to identify areas of genetic loss in carcinoma: allelotyping of polymorphic markers and representational difference analysis (RDA). This proposal aims to use these methods to further study the phenomenon of genetic loss in human carcinomas, to identify new tumor suppressor genes from areas of homozygous genomic deletion, and to characterize the genetic changes in pre-invasive precursor lesions of pancreatic carcinoma. Preliminary studies are provided for all aspects of this proposal. Drs. Leland Chung and joyce Hamlin will co-mentor the applicant; both have trained numerous graduate students and post-doctoral fellows, and have a long history of NIH grant support. Dr Hamlin is a Professor in the Dept. of Biochemistry, with an expertise in molecular genetic analysis of eukaryotic genomes. Dr. Chung is a Professor in the Dept. of Urology, with an expertise in cellular biology of human cancer. Together they provide the requisite experience in cancer biology and molecular genetic methodology to guide the applicant through the proposed research project and will aid the applicant in obtaining continuing finding during the later stages of this proposal. The applicant has secured a position of Asst. Professor in the Dept. of Pathology at the University of Virginia, which has committed lab space, funds for equipment and supplies, and technical support. The University of Virginia Hospital has an extensive frozen tumor bank and tissue procural procedures in place to support the research proposal. The applicant has shown competence in the field of molecular biology by publishing four first author peer-reviewed publications on DNA-protein interactions during his Ph,D training at Duke University. He has continued in scholarly pursuits during his subsequent clinical training at the National Institutes of Health and fellowship training at The Johns Hopkins University School of Medicine, with several abstracts and publications in diagnostic pathology and basic research. His long term goals are to establish himself as an independent investigator in the genetic basis of human carcinogenesis. The environment at The University of Virginia provides him with seminar series and participation in scientific journal clubs to remain current in the scientific literature, and forums for the presentation of his ongoing research for critical appraisal. Thr proposed project will establish for the applicant an independent research program and will provide him the training in personnel supervision and grant application that re necessary for a successful career in cancer research.